Our previous studies on active constituents of Nigella sativa have indicated that cell death induced by thymoquinone and alpha-hederin was dose- and time-dependent, in a range of four cancer cell lines. Both compounds elicited necrosis and apoptosis with a higher incidence of the latter induced by thymoquinone. As HEp-2 human laryngeal carcinoma cells were the most susceptible, we sought to bet...

Recently, loss of endogenous glutathione during N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxic injury, and the resultant overproduction of reactive oxygen species (ROS) through an arachidonic acid cascade process in brain, have been implicated in neuronal damage in various neurodegenerative diseases. Glutathione depletion induced by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor ...

In order to examine the role of glutathione (GSH), a key cellular antioxidant, on spontaneous tumor development, we tested the effects of buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, and 1,2-oxothiazolidine-4-carboxylic acid (OTCA), a cysteine and GSH precursor, on tumor incidence and spectrum in p53 nullizygous (p53-/-) transgenic mice. Mice were randomly assigned to th...

The renal dopaminergic system plays a significant role in controlling sodium excretion and blood pressure (BP). Overwhelming evidence shows that oxidative stress downregulates renal dopamine receptors (D1R), and antioxidant supplementation protects D1R function. However, the mechanisms for benefits of antioxidants in protecting D1R function are unknown. We investigated the role of nuclear facto...

The parasitic protozoa Trypanosoma brucei utilizes a novel cofactor (trypanothione, T(SH)2), which is a conjugate of GSH and spermidine, to maintain cellular redox balance. gamma-Glutamylcysteine synthetase (gamma-GCS) catalyzes the first step in the biosynthesis of GSH. To evaluate the importance of thiol metabolism to the parasite, RNAi methods were used to knock down gene expression of gamma...

A melphalan-resistant human rhabdomyosarcoma xenograft, TE-671 MR, was established in athymic mice by serial melphalan treatment of the parent xenograft, TE-671, at the 10% lethal dosage (LD10); significant resistance was evident after ten passages of the tumor. TE-671 MR demonstrated a doubling time of 3.5 days and a latency period to 1000-mm3 tumors of 27.5 days. The glutathione level of TE-6...

OBJECTIVES Buthionine sulfoximine (BSO) inhibits synthesis of glutathione as the main intracellular antioxidant. The aim of the present study is to investigate the effect of BSO-induced oxidative stress on histological structure of testis, testosterone secretion and semen parameters. MATERIALS AND METHODS Thirty male BALB/c mice were divided into 3 groups. In control group, the mice did not r...

Multidrug resistance-associated protein 2 (MRP2) is a member of a family of efflux transporters that are involved in biliary excretion of organic anions from hepatocytes. Disrupted canalicular localization and decreased protein expression of MRP2 have been observed in patients with chronic cholestatic disorder and hepatic failure without a change in its mRNA expression. We have previously demon...

Resistance to antineoplastic drugs is a major problem in the clinical management of cancer. Previous studies have demonstrated that the cytotoxicity of certain anticancer drugs is increased by lowering the glutathione (GSH) levels with buthionine sulfoximine (BSO), a specific inhibitor of •¿ v-glutamylcysteine synthetase. In this study we report that the resistance to doxorubicin, an anthracy...

BACKGROUND Changes in sulfhydryl (SH) compound availability may alter the hemodynamic effect of nitroglycerin (NTG). Data on the relation between NTG effect and thiol levels are, however, limited to in vitro experiments. The present study investigates how intracellular and extracellular changes in SH group concentrations (cysteine and glutathione [GSH]) affect the responsiveness to NTG in vivo....